We operate two clinical centers of Look AHEAD, a multicenter randomized clinical trial of weight loss for prevention of complications of type 2 diabetes. Since the clinical trial began in 2002, 5,145 volunteers with type 2 diabetes who were 45-76 years of age and overweight or obese (body mass index > 25 kg/m2) were enrolled in either the intensive lifestyle intervention (ILI) program or the diabetes support and education (DSE) program. The Diabetes Epidemiology and Clinical Research Section clinics enrolled 244 of these participants. The study has reported success in achieving and maintaining weight loss in the ILI group, while there was little weight loss on average in the DSE group. During the first four years after enrollment, the average weight losses were 6.2% in the ILI group and 0.9% in the DSE group. Effects of the weight loss on several health outcomes were reported in previous years. Several more health outcomes were reported during the current fiscal year. Cognitive function. We assessed whether randomization to 10 years of lifestyle intervention to induce and maintain weight loss improves cognitive function. Certified examiners who were masked to intervention assignment administered a standard battery of cognitive function tests (Modified Mini-Mental State Examination, Rey Auditory Verbal Learning Test, Digit Symbol Coding, Trail-Making Test, Modified Stroop Color-Word Test) to participants 10 to 13 years after enrollment. Assignment to lifestyle intervention was not associated with significantly different overall (P = .10) or domain-specific (all P > .10) cognitive function than assignment to diabetes support and education. Results were fairly consistent across prespecified groups, but there was some evidence of trends for differential intervention effects showing modest harm in ILI in participants with greater body mass index and in individuals with a history of cardiovascular disease. Cognitive function was not associated with changes in weight or fitness. In conclusion, a long-term behavioral weight loss intervention for overweight and obese adults with diabetes mellitus was not associated with cognitive benefit or harm.(3) Physical function. Lifestyle interventions have been shown to improve physical function over the short term; however, whether these benefits are sustainable is unknown. The long-term effects of an intensive lifestyle intervention on physical function were assessed in the Look AHEAD trial. Participants underwent standardized assessments of performance-based physical function including a 4- and 400-m walk, lower extremity physical performance (expanded Short Physical Performance Battery, SPPBexp), and grip strength approximately 11 years post-randomization and 1.5 years after the intervention was stopped (n=3,783). Individuals randomized to ILI had lower odds of slow gait speed (<0.8 m/sec) compared to those randomized to DSE (adjusted OR 95% CI: 0.84 0.71-0.99). Individuals randomized to ILI also had faster gait speed over 4-m and 400-m (adjusted mean difference 95% CI: 0.019 0.007-0.031 m/sec, p=0.002, and 0.023 0.012-0.034 m/sec, p<0.0001, respectively) and higher SPPBexp scores (0.037 0.011-0.063, p=0.005) compared to those randomized to DSE. The intervention effect was slightly larger for SPPBexp scores among older vs. younger participants (0.081 0.038-0.124 vs. 0.013 -0.021-0.047, p=0.01). An intensive lifestyle intervention has modest but significant long-term benefits on physical function in overweight and obese middle-aged and older adults with type 2 diabetes.(2) Left ventricular hypertrophy. Left ventricular hypertrophy assessed by electrocardiography (ECG-LVH) is a marker of subclinical cardiac damage and a strong predictor of cardiovascular disease (CVD) events. The prevalence of ECG-LVH is increased in obesity and type 2 diabetes; however, there are no data on the long-term effects of weight loss on ECG-LVH. We determined whether an intensive lifestyle intervention (ILI) reduces ECG-LVH in overweight and obese adults with type 2 diabetes. Data from 4,790 Look AHEAD participants (mean age: 58.8 6.8 years, 63.2% White) who were randomized to a 10-year ILI (n = 2,406) or diabetes support and education (DSE, n = 2,384) were included. ECG-LVH defined by Cornell voltage criteria was assessed every 2 years. Longitudinal logistic regression analysis with generalized estimation equations and linear mixed models were used to compare the prevalence of ECG-LVH and changes in absolute Cornell voltage over time between intervention groups, with tests of interactions by sex, race/ethnicity, and baseline CVD status. The Look AHEAD long-term lifestyle intervention did not significantly lower ECG-LVH in overweight and obese adults with type 2 diabetes.(1)